Studies of the clinical pharmacology of anticancer and antiretroviral drugs used to treat children with cancer and HIV-infection focus on new drug development and on the design of more rational approaches to the use of these agents based on the study of their pharmacokinetics and pharmacodynamics. The central nervous system (CNS) pharmacology of anticancer drugs and the identification of new treatment approaches for CNS tumors are emphasized. An integrated research program, which includes preclinical models to study the pharmacology of novel agents and an active clinical trials program to study the toxicity, activity, and pharmacology of these agents in children, is utilized. The CNS pharmacology of anticancer drugs is studied in a non-human primate model with indwelling ventricular catheters that allow for drug instillation into the ventricle and sampling of the cerebrospinal fluid (CSF). Drug penetration into the CSF, which serves as a surrogate measure of blood-brain barrier (BBB) penetration, is used to identify potential new drugs for CNS tumors. Drug penetration into brain and other tissues is also measured using microdialysis. In addition, new strategies to pharmacologically modulate the BBB are being investigated in this model. The preclinical and clinical development of new agents that can be administered intrathecally for the treatment of meningeal tumors is also focus of research. Clinical trials are performed as single institution studies or collaboratively with other childrens cancer centers or the cooperative groups. A variety of agents are studied, including classical cytotoxic drugs and drugs with novel mechanisms of action. Clinical pharmacokinetic studies focus on the development of pharmacokinetic models that allow for simulation of other doses and schedules, development of limited sampling strategies to simplify drug monitoring, and correlation with pharmacodynamic parameters, such as toxicity or response. New approaches to imaging and monitoring response in CNS tumors utilizing nuclear magnetic resonance spectroscopy and 3-dimensional image analysis, are incorporated into clinical brain tumor trials. The approach to the study of antiretroviral drugs in children parallels the approach to anticancer drugs. Preclinical pharmacokinetic studies are performed in the animal model with an emphasis on defining the CNS pharmacology of new antiretroviral agents, and clinical pharmacokinetic/pharmacodynamic studies are performed in children treated on clinical trials of new and existing antiretroviral drugs. The pharmacokinetics and pharmacodynamics of dideoxynucleosides, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors have been studied. - brain tumor, chemotherapeutics, childhood tumors, pharmacokinetics, pharmacology, microdialysis, - Human Subjects: Minor under 18 Years Old & Human Tissues, Fluids, Cells, etc.